This proposal is an interdisciplinary study that will attempt to clarify immunological and biochemical mechanisms and their potential interrelationships in the development of experimental pulmonary fibrosis induced by silica in the guinea pig. The guinea pig provides an excellent experimental model for pulmonary fibrosis since fibrotic (and granulomatous) lesions may be produced by direct instillation of silica into the tracheo-bronchial tree or by silica aerosolization. Furthermore, local lung and systemic immune properties have been well studied in this and other laboratories. Specifically, the proposal will focus on (1) serial morphologic and morphometric (and physiologic) studies in silica-exposed animals. (2) These results will be correlated with local and systemic immune abnormalities, including alterations in alveolar macrophage function (phagocytosis), recruitment and kinetics. (3) The role of macrophage-fibroblast interaction will also be examined with respect to macrophage factor(s) that may be responsible for the abnormalities in the lung's metabolism of connective tissue macromolecules. The latter will include parallel studies of possible qualitative and quantitative changes in (a) collagen types and (b) turnover rates for both collagen and elastin.